Review pubs.acs.org/IECR
Molecularly Imprinted Polymers for Clean Water: Analysis and Purification Xiantao Shen, Changgang Xu, and Lei Ye* Division of Pure and Applied Biochemistry, Lund University, Lund, Sweden ABSTRACT: Because of their predetermined selectivity, molecularly imprinted polymers (MIPs) have been extensively investigated to offer efficient separation of organic pollutants for water analysis and purification. In this review, we first describe the current development of water-compatible MIPs, and the physical encapsulation and chemical immobilization of MIP particles for practical applications related to water analysis and purification. We summarize the challenges in understanding the mechanisms in molecular imprinting, with a special emphasis on the use of nuclear magnetic resonance (NMR), dynamic light scattering (DLS), and synchronous fluorescence spectroscopy to gain theoretical insights into the molecular imprinting process. The highlighted synthetic methods and the mechanistic investigations discussed in this review should facilitate the identification of the most crucial factors affecting the applications of MIPs for clean water.
1. INTRODUCTION Clean water provides the foundation for prosperous communities. We rely on clean water to survive, yet right now we are facing a global water crisis of staggering proportions. To manage this crisis, new water resources (e.g., wastewater reclamation and reuse, seawater desalination, etc.) are suggested to support the daily need for clean water. Considering environmental protection, water quantity and quality, energy consumption and costs, wastewater reclamation and reuse has been considered one of the most important ways to provide a sufficient amount of clean water.1 Numerous standardized unit processes have been proposed to remove pollutants from wastewater, including chemical and biological oxidation, physical adsorption, sedimentation, and filtration.2 However, for some persistent organic pollutants (POPs), although municipal wastewater treatment plants can reduce POPs to some extent, the low-level POPs in the aqueous effluents may still cause a severe problem in the environment.3 For these reasons, new methods that are both selective and cost-effective to remove the low-level POPs are urgently needed. In this challenge, the central point is to prepare synthetic materials with specific molecular recognition ability targeted toward the pollutants. In biological processes, many essential biological interactions are governed by specific molecular recognition between biologically relevant molecules. Therefore, much attention has been focused on mimicking the biological processes, such as substrate−enzyme reactions, in order to generate artificial receptors based on synthetic materials.4 Among the various methods for fabricating artificial receptors, molecular imprinting is one of the most promising approaches, because molecularly imprinted polymers (MIPs) obtained from this technology have high molecular recognition selectivity, can be generated in a straightforward manner, and have outstanding thermal, mechanical, and chemical stability.5,6 In this case, molecular imprinting provides potential opportunities for efficient removal of low abundance pollutants with low cost, low energy consumption, and low environmental impact.7 © XXXX American Chemical Society
In this review, we focus on recent advances in the area of MIPs for clean water. Our special emphasis is on a new class of water-compatible MIPs generated by Pickering emulsion polymerization. Simultaneously, we pay special attention to the development of new conjugation chemistry that allows MIP nanoparticles to be immobilized on various supporting materials. Finally, we summarize the challenges in understanding the mechanisms and the theoretical aspects in molecular imprinting. We believe the synthetic methods and the mechanistic investigations discussed here will be useful to accelerate the practical applications of MIPs for clean water.
2. MOLECULAR IMPRINTING The history of molecular imprinting technology seems to be somewhat complicated. In the 1940s, by studying the mechanism of enzyme catalysis and antibody formation, Pauling first put forward the idea about molecular imprinting, which involved a protein antibody self-assembly with an antigen acting as a template.8 Later, Dickey (Pauling’s postdoctoral student) synthesized a type of substrate selective adsorbents via the precipitation of a mixture of silica gel and a template dye. After removal of the “patterning” dyes, the silica gel exhibited an increased affinity to the target dye.9,10 However, no significant advances in molecular imprinting have been made in the following 20 years. In 1972, Wulff et al. first demonstrated molecular imprinting in organic polymers by constructing a synthetic receptor using reversible chemical bonds between a template and functional monomers.11 In 1981, the idea of molecular imprinting was expanded to noncovalent systems by Mosbach and co-workers,12 who first prepared MIPs using noncovalent molecular interactions (such Special Issue: Recent Advances in Nanotechnology-based Water Purification Methods Received: September 26, 2012 Revised: November 14, 2012 Accepted: November 19, 2012
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often fail to bind target pollutants selectively in water,30 because the traditional polymers are often synthesized in organic solvent and display a different swelling effect when they are used in an aqueous system. The apparently different structure after swelling makes the MIPs unable to distinguish the target from other nontarget compounds.31 An early strategy to improving specific binding in water was by reducing nonspecific adsorption to MIPs. As first reported by Andersson et al.,32 by adding organic modifiers (e.g., surfactants or organic solvents), the nonspecific binding to hydrophobic MIPs in specific buffers could be minimized. A more interesting strategy is to solve the problem by developing new water-compatible MIPs to achieve selective molecular recognition in water. In biological systems, it is normal to achieve specific recognition in water. Therefore, careful consideration of the difference between traditional MIPs and biological macromolecules may help to improve the design and performance of MIPs under aqueous conditions. Looking back into the historical development of MIPs, researchers have paid much attention to enhance the strength of interactions between template and functional monomers by using anhydrous solvents,33 but hardly realized the important roles that water can play in achieving specific molecular recognition. It is wellknown that, in almost all biological systems, water is an integral part of biomacromolecules34 and contributes to maintain the stability and the function of functional proteins such as enzymes.35 Especially, the surrounding water of an enzyme is extremely important for the specific recognition of its substrate.36 The displacement of ordered water molecules makes the formation of an enzyme−substrate complex more thermodynamically favorable. As in biological systems, water molecules have been proven to play an important role in target binding by MIPs in a water environment. This phenomenon was first observed by Haginaka and co-workers.37 Considering that recognition of the template by the traditional MIPs is mainly mediated by hydrogen bonds between the template and the functional groups on the MIPs, and nonspecific adsorption is mainly caused by the hydrophobic or ion-exchange sites of the materials, Haginaka and co-workers managed to reduce the nonspecific adsorption in water by coating a hydrophilic external layer on the MIPs. The following-up studies indicated that the surface-modified MIPs can be applied to directly analyze (S)-naproxen and (S)-ibuprofen in serum,38 as well as β-blockers in biological fluids.39 Similarly, new restricted-access materials that combine MIPs with a hydrophilic external layer have been prepared to enable selective recognition of the corresponding templates.40,41 These results also indicate that the hydrophobic nonspecific interactions between the template and the polymeric matrices can be greatly reduced.42 To maintain target-specific binding in an aqueous solvent, MIPs with a core−shell structure have also been synthesized by Yang et al.43 The hydrophilic shell layer made of acrylamide (AA) and methacrylic acid (MAA) provided good water compatibility, resulting in decreased nonspecific binding in water (Figure 2). Recently, Pan et al. described the controlled synthesis of a series of water-compatible MIP microspheres with ultrathin hydrophilic poly(2-hydroxyethyl methacrylate) (PHEMA) shells. The hydrophilic layers were based on both PHEMA brushes and PHEMA hydrogel layer and were synthesized via surface-initiated reversible addition−fragmentation chain transfer (RAFT) polymerization.44
as hydrogen bonds, van der Waals forces, ionic interactions and hydrophobic effects) between template and functional monomers. Based on these pioneering studies, molecular imprinting technology started to grow rapidly.13 Molecular imprinting is a technology used to create molecular recognition sites that are chemically and sterically complementary to the target of interest in a synthetic polymer.14 The obtained MIPs are cross-linked polymeric materials that exhibit high binding capacity and selectivity against a target molecule (template). The concept of the imprinting process is schematically shown in Figure 1, which
Figure 1. Schematic representation of the principle of molecular imprinting. Adapted from ref 15.
consists of (1) formation of a complex between the template molecule and the monomers with appropriate functional groups, (2) polymerization by thermal or photo initiation, and (3) removal of the template molecule from the polymer matrix by physical or chemical methods, thus leaving specific binding sites in the bulk or on the surface of the polymers.15,16 MIPs have been synthesized with specific recognition ability for both chemical and biological molecules, such as drugs,17 pollutants,18 food ingredients,19 amino acids and proteins,20 various nucleotides, and their derivatives.21 These synthetic materials have been widely used in separation and purification science,22 chemical analysis and detection,23 catalysis,24 and drug delivery,25 as well as acting as plastic antibodies and receptors.26 Recently, Saridakis et al. described a new initiative in molecular imprinting, namely, the design of MIPs to assist protein crystallization.27 The results reported in this study represented a new niche for MIPs, which have promise to significantly accelerate the investigation of protein structures.28
3. NOVEL METHODOLOGIES TO SYNTHESIZE WATER-COMPATIBLE MIPS In wastewater, organic and inorganic pollutants often exist simultaneously. Molecular imprinting technology exhibits potential for selective removal of both inorganic and organic pollutants from water. In a very recent review, Mafu et al. critically discussed the synthesis, characterization, and applications of ion-imprinted polymers (IIPs) for separating toxic metal ions (including arsenic, selenium, copper, nickel, cobalt, aluminum, and their complexes).29 Therefore, in this review, we will focus on applications of MIPs to remove organic pollutants from water. At present, there are some limitations when MIPs are designed to remove organic pollutants directly from water. One of the most serious problems in this field is that MIPs B
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obtained MIP microspheres showed significant surface hydrophilicity and excellent molecular recognition ability in pure water.51 The above two approaches can be used to introduce a special structure (hydrophilic layer) onto MIPs, to enhance the selectivity of MIPs by decreasing nonspecific adsorption. However, the results do not support that water can play an active role in improving target binding. Only one research, based on NMR and calorimetry studies, showed direct proof that the interaction between a template compound and MIPs can be mediated by structured water molecules.52 Recently, a new approach that can introduce water molecules into the recognition process by controlling the fine structure of MIPs was proposed by Shen et al., making the MIPs to show specific recognition ability in water.53 The interfacial molecular imprinting was conducted in oil-in-water Pickering emulsions, where the molecular template was immobilized on the surface of SiO2 nanoparticles during the polymerization. After polymerization, the nanoparticles as well as the template were removed from the MIP particles to leave tiny indentations decorated with molecularly imprinted cavities (Figure 3a). The MIP microspheres generated in the Pickering emulsions had a well-controlled hierarchical structure and displayed group selectivity toward a series of chemicals under purely aqueous conditions (Figure 4). The molecular imprinting in Pickering emulsion has created surface imprinted sites on spherical MIP particles. In order to enhance the binding capacity and maintain the water compatibility of MIP microspheres, the actual molecular imprinting process was also confined in the interior of the monomer droplets in the oil-in-water Pickering emulsion (see Figure 3b).54 Because of the special partitioning of MAA between the oil phase and the water phase, the obtained MIP particles had a high density of carboxyl groups on their surface, which allowed the hydrophilic MIP microspheres to selectively recognize the template molecule in water. The porogen (toluene) used in the Pickering emulsion was important for the stability of the emulsion and the binding properties of the obtained MIP beads. Increasing the amount of porogen can decrease the stability of the emulsion, as well as increase the surface area and the nonspecific binding of the MIP beads.55 Under optimized conditions, the best imprinted polymer microspheres could recognize the template and its structural
Figure 2. One-pot synthesis of propranolol-imprinted core−shell nanoparticles. Step 1: propranolol-imprinted sites are generated by cross-linking polymerization between MAA and TRIM in the presence of the molecular template. Step 2: formation of hydrophilic shell by subsequent copolymerization with AAm and MBA. Adapted from ref 43.
The above research has revealed that a hydration layer surrounding the MIPs could be helpful to decrease nonspecific adsorption of compounds. However, water molecules are rarely involved in the molecular recognition process, making these modified MIPs not real mimics of biological antibody or enzyme. Alternatively, water molecules can be introduced into the binding sites of MIPs through more hydrophilic monomers. For example, a high-throughput method has been employed by Dirion et al. to optimize the preparation of water-compatible MIPs. As a result, the generated MIPs can be applied in pure aqueous environments.45 This achievement is originated from the hydrophilic copolymers, which can be wetted by water and exhibit low nonspecific adsorption in water. Using this method, Bolisay and co-workers also prepared MIPs that can recognize viruses in water.46 Similarly, the results obtained by both Shen et al.47 and Papy-Garcia et al.48 suggested that by modification with primary amines in the polymer, the obtained MIPs can specifically recognize their targets and barely bind the nontargets. As an improved method, hydrophilic macromolecules (such as chitosan49 and sugar moiety50) have been directly introduced into the imprinted polymers, and the resulting MIPs could separate L-glutamic acid or phenobarbital from dilute aqueous solution. Recently, Pan et al. demonstrated a facile and highly efficient one-pot approach to obtain narrowly dispersed water-compatible MIP microspheres by grafting hydrophilic polymers using reversible addition− fragmentation chain transfer (RAFT) polymerization. The
Figure 3. (a) Interfacial molecular imprinting procedure in SiO2-nanoparticle-stabilized Pickering emulsions. Step 1: polymerization; Step 2: removal of silica and template. Reprinted from ref 53. Copyright 2011, American Chemical Society. (b) Schematic illustration for the synthesis of MIP microspheres via Pickering emulsion polymerization. (Reprinted from ref 55. Copyright 2012, Royal Society of Chemistry.) C
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Figure 4. SEM images of the polymer microspheres before (a) and after (b) the silica particles have been removed. Panel (c) shows the uptake of atenolol (I), metoprolol (II), pindolol (III), and propranolol (IV) by MIP-I and MIP-II. MIP-I and MIP-II were imprinted against the isopropylaminopropanediol and aminopropanediol moieties, respectively. Reprinted from ref 53. Copyright 2011, American Chemical Society.
completely remove endocrine disrupting chemicals (EDCs, 2 μg L−1) from wastewater, whereas only 49%−74% of EDCs could be removed with the nonimprinted polymers (prepared without a template).58 The method used in this work is a promising way to resolve the clogging problem when MIPs must be used as column packing materials. This type of monolith is a novel, cost-effective sorbent, allowing fast processing of particulate-containing fluids, and it is very attractive in application areas such as environmental remediation. The new composite imprinted adsorbents can process large volumes of effluents at a high flow rate without losing their binding efficiency. As an example, it was shown that 100% of 17β-stradiol and 86% of atrazine could be removed from spiked water in a recycling mode with a very short retention time (4 min) in a moving-bed reactor.59 Recently, Ö nnby et al. reported three types of macroporous cryogels: (a) aluminum nanoparticles (Alu-NPs,
